Protective effect of a 21-aminosteroid against hemorrhage-induced ischemia-reperfusion injury in the rat stomach: role of lipid peroxidation.

We investigated the role that lipid peroxidation plays in a hemorrhage-induced ischemia-reperfusion model of gastric injury. Rats were pretreated with an inhibitor of this process, a 21-aminosteroid (U-74389G, 10 mg/kg), or an appropriate control solution intravenously 15 min prior to 20 min of ischemia, followed by 20 min of reperfusion. Results indicated that U-74389G pretreatment significantly attenuated gastric damage compared with corresponding control animals (19.8 vs. 176.8 mm2, p < .001). Enaldehyde levels (picomoles/mg protein), a biochemical index of lipid peroxidation, paralleled these injury findings (12 vs 960, p < .001). Histologically, U-74389G pretreatment almost completely prevented gastric injury compared to control stomachs. Additional studies revealed that lipid peroxidation preceded the formation of gastric damage, and injury occurred predominantly during reperfusion, because animals subjected to ischemia alone without reperfusion failed to develop appreciable injury or enhanced enaldehyde formation. Further, if U-74389G was given intravenously after ischemia, but prior to reperfusion, gastric injury and enaldehyde formation were similarly attenuated. Our findings are consistent with the hypothesis that lipid peroxidation likely plays an important role in hemorrhage-induced ischemia-reperfusion injury to the stomach.